VATIS UPDATE Article

In a study, researchers at the Medical University of South Carolina (MUSC), the United States, have reported the cell’s response to unfolded or misfolded proteins as a cause, rather than a consequence, of metabolic disorders. In an article published by Nature Structural & Molecular Biology, the researchers identified a little-known molecule as the trigger for this response.

When improperly folded molecules are encountered in cells, the unfolded protein response (UPR) is activated within the endoplasmic reticulum (ER). The ER is in charge of molecular quality control, making sure proteins, lipids and other molecules are folded properly before the cell attempts to use them for metabolic processes. Here, a master protein called grp78 is in contact with three main signaling hubs that make up the control center of the UPR.

When an unfolded or misfolded protein is encountered by grp78, it breaks contact with those sensors and activates the UPR. The UPR then refolds or disposes of such molecules before they are shipped to the parts of the cell that need them. CNPY2 has been known for some time to reside within the ER, but its function there has remained a mystery. To start, mice without CNPY2 were generated to see how they would grow.